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Biomedical subjects

L M Ruilope

Publications and source records attributed to L M Ruilope.

At least 91 records · Page 5Linked to original sources
PubMed1997

Effects of UP269-6, a new angiotensin II receptor antagonist, and captopril on the progression of rat diabetic nephropathy.

To estimate the effects of UP269-6, a nonpeptide angiotensin II receptor antagonist, and captopril, a converting enzyme inhibitor, on the progression of nephropathy, 77 uninephrectomized diabetic rats were maintained for 8 months with plasma glucose levels from 300 to 500 mg/dL. Systemic and renal parameters were periodically measured, and, at the time of death, a histological evaluation of renal damage was performed. Control rats (no additional treatment but insulin) showed increased blood pressure and urinary albumin levels, together with prominent alterations in the kidney (renal and glomerular hypertrophies, tubular atrophy, and 19% of sclerotic glomeruli). Captopril (50 mg/kg/day) and UP269-6 (10 mg/kg/day) reduced blood pressure and albumin excretion levels, and improved histological renal preservation (lower renal and glomerular hypertrophies, tubular atrophy, and percentage of sclerotic glomeruli: 5% and 7%, respectively). Finally, a low dose of UP269-6 (1 mg/kg/day), which induced an intermediate level of blood pressure between control and the other treated groups, produced an equivalent degree of nephroprotection. Our data demonstrate the efficacy of this new angiotensin II receptor antagonist on the progression of diabetic renal damage. These results also reinforce the role attributed to angiotensin II in the development of renal derangement in this model, as UP269-6 is devoid of agonistic effect on the kinin system.

Albuminuria↗
PubMed1997

How should we treat hypertensive women with cardiac and renal impairment?

Arterial hypertension is the most common chronic medical condition requiring office visits to physicians and is a major contributing factor to the development of myocardial infarction and stroke. Its importance as a cardiovascular risk factor is at least as significant in women as in men; however, the ever-growing literature on hypertension shows surprisingly little data concerning sex differences. Large clinical trials of antihypertensive treatment have not clearly demonstrated gender differences in blood pressure response and outcome, but the majority of patients in these trials were men. Even so, some evidence indicates that white women treated for hypertension obtain less benefit than men. The pathophysiology of hypertension in men and women is similar in many aspects, but important gender differences are now emerging. Studies designed to clarify these differences are required, as a better knowledge of the underlying mechanisms will allow for a more precise stratification of risk and a more accurate approach to both nonpharmacologic and pharmacologic treatment.

Adrenergic beta-Antagonists↗
PubMed1997

Renoprotection and renin-angiotensin system blockade in diabetes mellitus.

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in the United States, and accounts for 35% of all the patients with ESRD entering a dialysis program; 63% of patients with diabetic nephropathy have type II diabetes mellitus. Hypertension is a major risk factor for renal disease and is common in people with diabetes mellitus. Strategies for preventing the progression of renal failure in patients with diabetes mellitus include glycemic control, and control of blood pressure. Blocking the renin-angiotensin system (RAS) slows the progression of established diabetic nephropathy in type I diabetes mellitus, and inhibiting angiotensin II formation retards or impedes the progression from microalbuminuria to established diabetic nephropathy (macroproteinuria) in people with type I diabetes mellitus. The situation could be the same for people with type II diabetes mellitus. The ability of RAS blockade using irbesartan, an AT1 angiotensin II receptor antagonist, to slow the progression in renal failure has been compared with that of the calcium channel blocker amlodipine and placebo in a pilot study. The results suggest that blockade of the RAS, in this case with irbesartan, is at least equivalent to calcium channel blockers with respect to antihypertensive efficacy, but provides better renoprotective benefits.

Amlodipine↗
PubMed1997

L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients.

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.

Adult↗
PubMed1997

How far should blood pressure be reduced in diabetic hypertensive patients?

EPIDEMIOLOGY OF DIABETES: Diabetes mellitus and arterial hypertension are closely related diseases that strongly predispose an individual to atherosclerotic cardiovascular disease and to renal failure. High blood pressure is twice as frequent in diabetics compared with the general population, and often precedes and contributes to the development of diabetic nephropathy. The prevalence of coexisting arterial hypertension and non-insulin-dependent diabetes mellitus (NIDDM) is increasing as populations age, giving an increased prevalence of both diseases. TREATMENT OF HYPERTENSIVE DIABETIC PATIENTS: The goal of treating arterial hypertension in diabetic patients is to prevent death and disability associated with high blood pressure. In addition, other reversible risk factors for cardiovascular disease, seen so frequently in hypertensive diabetics, also need to be addressed. The optimal goal of blood pressure control in diabetics has not been established, but there are indications that it should be lower than the 130/85 mmHg systolic/diastolic pressure recommended by current guidelines. In the presence of multiple associated risk factors, most guidelines suggest a threshold for intervention of > or = 140/90 mmHg. In particular, in hypertensive diabetic patients intervention must be early and aggressive.

Blood Pressure↗
PubMed1997

Endothelial dysfunction in spontaneously hypertensive rats: consequences of chronic treatment with losartan or captopril.

BACKGROUND: Hypertension is associated with endothelial dysfunction characterized by decreased endothelium-dependent relaxations and increased endothelium-dependent contractions. Angiotensin converting enzyme inhibitors and thromboxane A2 receptor antagonists decreased the endothelium dysfunction in hypertensive animals. OBJECTIVE: To investigate the effects of prolonged treatment with losartan on endothelium-dependent and -independent relaxations and contractions in aortic rings from spontaneously hypertensive rats (SHR). MATERIAL AND METHODS: Male SHR aged 16 weeks were treated for 12 consecutive weeks either with 10 mg/kg losartan per day or with 60 mg/kg captopril per day administered via their drinking water. The systolic blood pressure was evaluated basally and during week 12. At the end of the treatment period, the vascular reactivity in aortic rings was studies. A group of rats treated with captopril was studies as a reference group. RESULTS: Losartan and captopril reduced the blood pressure significantly and comparably. Both drugs enhanced acetylcholine-induced relaxations and reduced the maximal contractile response to acetylcholine in the presence of NG-nitro-L arginine methyl ester (L-NAME). Contractile responses to phenylephrine, endothelin-l and U46619 were not affected by these treatments. Increased relaxing responses to superoxide dismutase were observed only in captopril-treated rats. Losartan reduced the contractile response to angiotensin II. By contrast this contractile response was elevated in rats treated with captopril. CONCLUSIONS: Prolonged antihypertensive treatments with losartan and captopril decreased the endothelial dysfunction in aortic rings from SHR not only by enhancing NO-dependent relaxations but also by reducing the contractions in response to an endothelium-derived contracting factor. The results further confirm that an endothelium-derived contracting factor plays a role in vascular dysfunction in SHR and the relationships between this factor and angiotensin II.

Acetylcholine↗
PubMed1997

Losartan reduces constrictor responses to endothelin-1 and the thromboxane A2 analogue in aortic rings from spontaneously hypertensive rats: role of nitric oxide.

OBJECTIVE: Our study was designed to investigate whether angiotensin II subtype 1 (AT1) receptors are involved in the constrictor responses evoked by endothelin-1 and the thromboxane A2 analogue U46619 in aortic rings from spontaneously hypertensive rats (SHR), by studying the effect of the AT1 receptor antagonist losartan. In addition, since nitric oxide seems to participate in the mechanism of action of losartan, we studied the effect of the nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the action of losartan. MATERIALS AND METHODS: Dose-response curves of either endothelin-1 (10(-10) to 10(-7) mol/l) or U46619 (10(-10) to 10(-6) mol/l) were studied in the presence or absence of losartan (10(-5) mol/l) in aortic rings from SHR. Likewise, similar experiments were done in aortic rings pretreated with the nitric oxide synthesis inhibitor, L-NAME (10(-4) mol/l). RESULTS: Pre-incubation with losartan significantly reduced the contractile response to endothelin-1 compared with control rings, without modifying the value represented by 50% of the maximal response (pD2). The concentration-response curve to U46619 was shifted to the right in the presence of losartan, reducing the pD2 compared with control rings. The presence of captopril (10(-5) mol/l) in the incubation media did not alter the response to either endothelin-1 or U46619. The diminished response to both endothelin-1 and U46619 in the presence of losartan was reversed in L-NAME-pretreated rings. CONCLUSIONS: Angiotensin II seems to participate in the vasoconstriction induced by both endothelin-1 and the thromboxane A2 analogue through the stimulation of AT1 receptors in SHR aortic rings, because losartan inhibited this effect. Moreover, nitric oxide appears to be involved in this action of losartan.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

The natriuretic effect of nifedipine gastrointestinal therapeutic system remains despite the presence of mild-to-moderate renal failure.

BACKGROUND: Calcium channel blockers facilitate the renal excretion of sodium and this effect is maintained during chronic administration of these drugs. However, it is unknown whether this natriuretic effect remains despite the presence of a decreased renal function. OBJECTIVE: To compare the natriuretic capacity of nifedipine gastrointestinal therapeutic system (GITS) and lisinopril in patients with mild-to-moderate chronic renal failure. METHODS: An open-label, randomized, comparative study was conducted to compare the natriuretic capacity of nifedipine GITS and lisinopril in the presence of mild-to-moderate renal failure (creatinine clearance 30-80 ml/min). After a wash-out period of 4 weeks an intravenous saline infusion (30 ml/kg of body weight of isotonic saline in 4 h) was performed and repeated after 4 weeks of active therapy. Two sex- and age-matched groups of hypertensive patients (n = 25) were included in the study. Renal failure was diagnosed as secondary to nephrosclerosis in all the patients. RESULTS: A significant increase in the renal capacity to excrete the sodium load was observed in patients receiving nifedipine GITS (n = 11) but not in those taking lisinopril (n = 13). Both drugs controlled blood pressure to a similar extent. No changes were observed in body weight, glomerular filtration rate and renal plasma flow (measured as inulin and paraaminohippurate clearances). A significant drop was observed in urinary albumin excretion after lisinopril, but not after nifedipine. Heart rate was higher in nifedipine group. CONCLUSION: The natriuretic capacity of nifedipine GITS remains despite the presence of mild-to-moderate chronic renal failure. Such an effect takes place in the absence of changes in renal hemodynamics, suggesting that it is caused by a direct tubular effect.

Administration, Oral↗
PubMed1997

Renal implications of arterial hypertension.

Renal vascular damage caused by arterial hypertension participates in alterations of the systemic vascular function and structure. Nephrosclerosis seems to run in parallel with the systemic atherosclerosis that accounts for the increased cardiovascular morbidity and mortality seen in hypertensive patients. Parameters indicating the existence of an alteration in renal function (increased serum creatinine, proteinuria and microalbuminuria) are independent predictors for an increased cardiovascular morbidity and mortality. Hence, parameters of renal function must be considered in any stratification of cardiovascular risk in hypertensive patients.

Albuminuria↗
PubMed1997

Surrogate endpoints and renal protection: focus on microalbuminuria.

End-stage renal disease (ESRD) is a major public health problem worldwide. The past decade has witnessed increased interest and investigative attention on therapeutic manoeuvres to retard the progression of renal disease. Reduction of albuminuria is regarded as a surrogate endpoint, because this phenomenon seems to be associated with preservation of GFR (principal endpoint) in diabetic nephropathy. Studies from our laboratory suggest that reduction in albuminuria during ACE inhibition constitutes a predictor of an attenuated rate of decline in GFR in early diabetic nephropathy. Because the rate of decline in kidney function is used to assess prognosis and the efficacy of therapy on progression of renal disease, a valid method for the determination of GFR is essential. During the last two decades, several radioactive and non-radioactive filtration markers have been validated and found to be both accurate and precise compared to inulin. Plasma clearance of such filtration markers is frequently applied in clinical trials in diabetic nephropathy because patients suffering from this complication frequently also suffer from diabetic cystopathy, precluding measurements of urine volume. Measurements of serum creatinine, creatinine clearance, calculated creatinine clearance by use of the Cockroft-Gault formula must all be regarded as surrogate measurements for glomerular filtration rate. Consequently, care must be taken to select appropriate filtration markers in order to rigorously evaluate therapeutic trials in progressive renal disease.

Albuminuria↗
PubMed1996

Effects of antihypertensive drugs on blood pressure and metabolic alterations in the fructose-induced hypertensive rat.

Fructose feeding induces a moderate increase in blood pressure (BP) levels in normal rats, which is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. Increased vascular resistances in skeletal muscle have been proposed to contribute to BP elevation and insulin resistance in this animal model. To further explore the mechanisms underlying the fructose-induced hypertension in rats, the effects of quinapril and diltiazem on BP, renal function, plasma levels of glucose, insulin, and triglycerides, and insulin resistance were studied. Male Sprague-Dawley rats were fed for 4 weeks with diets containing 60% fructose or 60% starch and received quinapril or diltiazem in the drinking water. Fructose-fed rats showed higher BP and plasma levels of insulin and triglycerides when compared to controls. Treatments with quinapril or diltiazem prevented BP elevation and reduced elevated plasma insulin levels in fructose-fed rats. Plasma glucose and insulin levels were higher (P < .05) in fructose-fed rats than in controls at 15, 30, and 60 min after oral glucose load. Treatments with either quinapril or diltiazem prevented the exaggerated plasma insulin and glucose levels in response to oral glucose load in fructose-fed rats. In summary, both quinapril and diltiazem were able to prevent BP elevation levels in the fructose-fed rat, and reduced the exaggerated response to an oral glucose tolerance test in these animals.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Effects of L-arginine infusion on renal hemodynamics and sodium excretion during hypo-, normo-, and hyperinsulinemia, as studied in dogs.

The response of renal hemodynamics and sodium excretion (NaU) to an infusion of L-arginine, in the presence (experiment I) or absence (experiment II) of endogenous insulin secretion and during a sustained hyperinsulinemic euglycemic state (experiment III), was studied in 10 age-matched beagle dogs. The experiments were preceded by a standard oral glucose tolerance test (OGTT), performed 1 week before experiment I. One week resting periods were allowed between experiments I, II, and III. No differences in renal hemodynamics and NaU were observed between basal (experiment I) and insulin secretion suppressed states (experiment II). L-Arginine infusion increased renal plasma flow (RPF), glomerular filtration rate (GFR), and NaU to a similar extent in both experiments. The hyperinsulinemic-euglycemic state (experiment III) induced a decrease in renal hemodynamics and NaU. In this situation, the infusion of L-arginine increased NaU, but was unable to increase RPF and GFR. Our data suggest that a sustained hyperinsulinemic state can interact with the physiological vasoactive mechanisms involved in the regulation of renal vasculature. These results may be pertinent to human disease, especially in pathological conditions in which insulin resistance is present.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Renal and vascular consequences of the chronic nitric oxide synthase inhibition. Effects of antihypertensive drugs.

The effects of the administration of either the angiotensin converting enzyme (ACE) inhibitor, quinapril (10 mg/kg/day, orally), or the calcium antagonist, diltiazem (100 mg/kg/day, orally), on blood pressure (BP), renal function, and vascular reactivity in isolated perfused mesenteric beds were studied in rats treated for 8 weeks with the nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (LNAME, 40 mg/kg/day). The oral administration of LNAME significantly increased systolic BP values, which reached the levels of 186 +/- 7 mm Hg at week 8. Both quinapril and diltiazem reduced this, although the ACE inhibitor was more effective than the calcium antagonist. The chronic inhibition of NO resulted in an increase in water excretion whether or not the increase in systolic BP was prevented by the coadministration of either quinapril or diltiazem. At the end of the experiment, LNAME-treated rats presented higher proteinuria than control rats (140 +/- 4 mg/24 hours v 21 +/- 1 mg/24 hours, P < .05). This elevated protein excretion was normalized by both antihypertensive drugs. None of the treatments was able to modify either natriuresis or plasma creatinine levels. Endothelium-dependent relaxations to acetylcholine (10(-12) to 10(-8) mol/L) were comparable in all groups. However, the vasoconstriction induced by either the continuous infusion of phenylephrine (10(-5) mol/L) or by a bolus of angiotensin II (1 nmol) was higher in the animals that received LNAME than in control ones. The antihypertensive therapy normalized the response to phenylephrine but not to angiotensin II. These data suggest that both quinapril and diltiazem are not only able to reduce BP elevation induced by the chronic administration of LNAME in rats, but also to prevent the renal damage and the hyperresponsiveness to phenylephrine induced by this NO synthesis inhibitor.

Angiotensin-Converting Enzyme Inhibitors↗